NDLI: IL-12 Is Required for Anti-OX40-Mediated CD4 T Cell Survival

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IL-12 Is Required for Anti-OX40-Mediated CD4 T Cell Survival

Content Provider	Scilit
Author	Ruby, Carl E. Montler, Ryan Zheng, Rongxui Shu, Suyu Weinberg, Andrew D.
Copyright Year	2008
Description	Engagement of OX40 greatly improves CD4 T cell function and survival. Previously, we showed that both OX40 engagement and CTLA-4 blockade led to enhanced CD4 T cell expansion, but only OX40 signaling increased survival. To identify pathways associated with OX40-mediated survival, the gene expression of Ag-activated CD4 T cells isolated from mice treated with anti-OX40 and -CTLA-4 was compared. This comparison revealed a potential role for IL-12 through increased expression of the IL-12R-signaling subunit (IL-12Rβ2) on T cells activated 3 days previously with Ag and anti-OX40. The temporal expression of IL-12Rβ2 on OX40-stimulated CD4 T cells was tightly regulated and peaked ∼4–6 days after initial activation/expansion, but before the beginning of T cell contraction. IL-12 signaling, during this window of IL-12Rβ2 expression, was required for enhanced T cell survival and survival was associated with STAT4-specific signaling. The findings from these observations were exploited in several different mouse tumor models where we found that the combination of anti-OX40 and IL-12 showed synergistic therapeutic efficacy. These results may lead to the elucidation of the molecular pathways involved with CD4 T cell survival that contribute to improved memory, and understanding of these pathways could lead to greater efficacy of immune stimulatory Abs in tumor-bearing individuals.
Ending Page	2148
Page Count	9
Starting Page	2140
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.180.4.2140
Alternate Webpage(s)	http://www.jimmunol.org/content/180/4/2140.full.pdf
Journal	The Journal of Immunology
Issue Number	4
Volume Number	180
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2008-02-15
Access Restriction	Open
Subject Keyword	Gene Expression Anti Ox40 Cd4 T Cell
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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